Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000277.3(PAH):c.1156T>G (p.Tyr386Asp)

Curation Version - 1.0
Curation History
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CA229361

102537 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 428af0db-e5b5-4ac8-8ef3-d61055a45a3a

Approved on: 2022-06-24

Published on: 2022-06-28

HGVS expressions

NM_000277.3:c.1156T>G

NM_000277.3(PAH):c.1156T>G (p.Tyr386Asp)

NC_000012.12:g.102843689A>C

CM000674.2:g.102843689A>C

NC_000012.11:g.103237467A>C

CM000674.1:g.103237467A>C

NC_000012.10:g.101761597A>C

NG_008690.1:g.78914T>G

NG_008690.2:g.119722T>G

ENST00000553106.6:c.1156T>G

ENST00000307000.7:c.1141T>G

ENST00000549247.6:n.915T>G

ENST00000551114.2:n.818T>G

ENST00000553106.5:c.1156T>G

ENST00000635477.1:n.260T>G

ENST00000635528.1:n.671T>G

NM_000277.1:c.1156T>G

NM_000277.2:c.1156T>G

NM_001354304.1:c.1156T>G

NM_001354304.2:c.1156T>G

Likely Pathogenic

PM3_Supporting PP4 PP3 PM5 PM2

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.1156T>G (p.Tyr386Asp) variant in PAH has been reported in 1 female, Italian patient - type of PKU not specified, serum Phe = 822umol/L; BH4 responsiveness was not specified (PMID: 23430918; PP4). This variant has been detected with R158Q - reported as pathogenic in ClinVar (VarID:587), 14 submitters, phase unknown - 0.5 points (PMID: 23430918; PM3_Supporting). Another missense change at the same amino is pathogenic (p.Tyr386Cys). This variant is absent from population databases (PM2) and is predicted deleterious by SIFT, PolyPhen2, MutationTaster, and REVEL = 0.977 (PP3). In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM5, PP3, PP4, PM3_Supporting.

PM3_Supporting

PMID: 23430918 - Y386D detected with R158Q - reported as pathogenic in ClinVar (VarID:587), 14 submitters, phase unknown - 0.5 points

PP4

PMID: 23430918 - Y386D reported in 1 female, Italian patient - type of PKU not specified, serum Phe = 822umol/L; BH4 responsiveness was not specified

PP3

Predicted deleterious by SIFT, PolyPhen2, MutationTaster, and REVEL = 0.977.

PM5

At the same codon as c.1157A>G (p.Tyr386Cys) pathogenic by ClinGen PAH VCEP

PM2

Variant absent from population databases.

Curation History

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